The long-term goals of this ICIDR are to advance our understanding of the role of transmission dynamics, host immunity, and parasite genetic structure in the pathogenesis of bancroftian filiariasis. The research program takes advantage of well-established field sites for clinical, epidemiological, and laboratory studies of bancroftian filariasis in Papua New Guinea and Kenya. The three interrelated projects are focused on: I. Transmission as a determinant of immunity and lymphatic pathology in bancroftian filariasis. This work will examine the influence of transmission intensity on infection burden, lymphatic pathology, and T-cell and allergic- type responses at the population level in Papua New Guinea. 2. Prenatal sensitization to Wuchereria bancrofii and its impact on infection and immunity in children. This work will examine how in utero sensitization or tolerance to W. bancrofii influences the response to filarial infection and childhood vaccines in Kenya. 3. Spatial ecology of transmission and heterogeneity of infection and lymphatic pathology in bancroftian filariasis. This work will examine the impact of spatial heterogeneity of vector biting patterns on W bancrofii infection burden and lymphatic disease at the household and individual level. These studies will advance knowledge of key ecologic and clinical features of filariasis which are critical for the evaluation of current approaches to elimination this disease at a global level.